This poster was presented by Gattefossé at CRS 2025, the Annual Meeting and Exposition conference 2025 in Philadelphia, PA:
Introduction
Amorphous solid dispersion (ASD) is one of the most promising strategies to address the bioavailability issues faced by poorly soluble Active Pharmaceutical Ingredients (API). On the other hand, surfactants can also improve API solubility but remain challenging to incorporate in tablets. Incorporation of a surfactant into a binary ASD (API and polymer) to develop a ternary ASD is an emerging trend1 to further increase the solubility, the bioavailability and the stability of ASD while maintaining the possibility to manufacture a tablet dosage form.
In our previous work, we prepared ticagrelor ternary ASD by Hot Melt Extrusion (HME) and tested the obtained extrudates, showing the amorphization of the active in the binary and ternary ASDs.
We also showed a strong decrease in the extrusion temperature, and a higher API dissolution compared to binary extrudates and neat API.
In this study, we formulated and tested tablets prepared either from those ternary extrudates, or from binary extrudates, or from binary physical mixture (polymer and API).
Materials and Methods
Ticagrelor, used as a model API (BCS class IV with 60 or 90 mg of therapeutic dose), was purchased from Nantong Chanyoo Pharmatech. Polyvinylpyrrolidone vinyl acetate (copovidone / PVP-VA), used as a polymer, was provided by Ashland, while Gelucire® 48/16, utilized as a surfactant, was provided by Gattefossé.
Ternary extrudate contained 14.3% ticagrelor, 21.4% Gelucire® 48/16 and 64.3% copovidone, while binary extrudate contained 25% ticagrelor and 75% copovidone. The batches were extruded with standard twin-screw configuration (Pharma 11 from Thermo Scientific™), a 2-mm die, a screw speed of 50 rpm and a feed rate of 150 g/h. The extrudates were grinded to obtain a powder (around 500 μm particle size average).
The other tableting excipients, mannitol, silicified microcrystalline cellulose, crospovidone and magnesium stearate were provided by Roquette, JRS Pharma, BASF, and Sigma Aldrich, respectively. The internal phase was first mixed, followed by the external phase, using a Turbula blender. Tablets were manufactured using a NanoStyl’One (MEDELPHARM) simulator press. The different formulations are gathered in Table 1.
The API release was determined by in vitro dissolution testing (USP II, phosphate buffer pH 6.8, 900 mL) followed by high performance liquid chromatography (HPLC) analysis. The tablets were stored at 25°C/60%relative humidity (RH) for 3 months and release profile stability was assessed.
Table 1. Composition of tablets
Results
The addition of Gelucire® 48/16 significantly reduces the extrusion temperature, as shown in Table 2.
The tablets obtained weighed 600 mg and presented different aspects (Figure 1): tablets with binary extrudate looked matte with grey spots, tablets with ternary extrudate looked shiny with grey spots and tablets with binary physical mixture had heterogenous matte surface.
ternary extrudate / right: tablets with physical mixture).
During in vitro dissolution testing, an increase in the dissolved API quantity was measured for tablets manufactured with binary ASD (18%) compared to neat API (8%) and physical mixture tablets (10%). When Gelucire® 48/16 was added, in the ternary ASD tablet, the API release reached 92%: it represents a 5-fold and 9-fold increase compared to binary ASD tablets and physical mixture tablets respectively (Figure 2).
The decrease of the API cristallinity in binary ASD tablets led to a slight increase of the percentage dissolved, but still limited, whereas the combination of amorphization and solubilization in the ternary ASD tablets achieved a full dissolution of the active. The dissolution profile of the tablets remained unchanged after storage at 25°C/60% RH for 3 months.
Conclusion
Ternary ASD extrusion is a convenient way to incorporate lipid-based surfactants in tablets. The proposed ternary ASD tablet formulation, prepared from extrudates containing Gelucire® 48/16 and PVP-VA increases dramatically the release of a BCS class IV API.
See the full poster on Ticagrelor Amorphous Solid Dispersion tablets here
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Source: Gattefossé, Poster Ticagrelor Amorphous Solid Dispersion tablets, Elsa GATTEFOSSE, Diane SCHNEIDER, Cédric MIOLANE, Karan SIYODIA, Philippe CAISSE,
